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The story of the game is based on Robert Louis Stevenson's story. Dr. Jekyll is on his way to his wedding with the Miss Millicent.[2] The game's ending depends on which character, Jekyll or Hyde, reaches the church first.[citation needed]

As Dr. Jekyll walks to the church with his cane in hand, several townspeople, animals, and other obstacles obstruct his path, causing him to become angry.[3] After your stress meter fills up, Dr. Jekyll will transform into Mr. Hyde. The gameplay then moves to a demonic world, where Hyde will fire out a "psycho wave" at enemies.[2] The Psycho Wave is in fact proudly displayed on the game's cover.[4] If his anger reaches a certain level, he transforms into Mr. Hyde and is taken to a nightmarish world of monsters. As Mr. Hyde kills these monsters, his anger abates and eventually he transforms back into Dr. Jekyll.[3]

The game features six levels, but the levels differ between the Japanese and North American versions. The Japanese version follows this order: City, Park, Alley, Town, Cemetery, Street. However, the North American version replaces a few levels and follows this order: Town, Cemetery, Town, Park, Cemetery, Street. The North American version also removed certain sprites and segments from the original Japanese version.

The player starts out controlling Dr. Jekyll on his way to the church, walking to the right. As he takes damage from the various enemies and obstacles, his Life Meter decreases and his Anger Meter increases. If his Life Meter is fully depleted, Dr. Jekyll dies and the game is over. If his Anger Meter completely fills, however, he transforms into Mr. Hyde. Day turns to night and monsters appear. At this point, the level is mirrored horizontally and Mr. Hyde walks from right to left with the screen autoscrolling. Mr. Hyde must kill monsters as fast as he can in order to turn back into Dr. Jekyll, with Shepp monsters generally giving the largest refill to his Meter, though killing other monsters may refill the Meter a small amount.

If at any point Mr. Hyde reaches Dr. Jekyll's location (except in the final segment), a bolt of lightning strikes him, which kills him instantly. Therefore, the objective of the game is to advance as far as possible as Dr. Jekyll and to transform back as soon as possible as Mr. Hyde. However the more detailed alternate ending of the game requires the player to strategically reach the Church with Mr. Hyde but making sure Dr Jekyll stays ahead of Mr. Hyde until the final level.[3]

Upon release, Famitsu gave it a score of 19 out of 40.[1]Aktueller Software Markt gave the game an overall score of 30 out of 50. The reviewer hoped that the game would soon become available in the German market, despite its small shortcomings.[5]

The game has gone on to become infamous, with reviewers citing bad graphics, confusing gameplay, and poor use of the characters and setting. Darrell Monti of Nintendo Life called it one of the worst games he got for the NES.[6] In 2004, Game Informer reviewed the game in their Retro Reviews section and gave it a 5 out of 10, ending the review by saying "Flawed on every fundamental level, Dr. Jekyll and Mr. Hyde is possibly the most unplayable garbage available on the NES."[7]

In 2018, Eurogamer placed the game as number 8 on their list of top ten worst games of the 80s. The writers complained that nothing is explained to the player, and that some characters harm the player, but some do not. They called it is a frustrating and confusing experience.[4]IGN ranked the cover art the third scariest cover art in gaming.[8]